Hierarchically Engineered Phage-Activated Click Interface for Ultra-Efficient Cell Capture

Efficient cell adhesion under flow is vital in biological processes and artificial capture systems governed by the frequency of cell-surface encounters and the probability of successful binding. While previous efforts mainly focused on enhancing these factors at the molecular level within two-dimensional interfaces, strategies that simultaneously boost both aspects across the multiscale spatial level remain largely unexplored. In this study, we developed a multiscale hierarchically engineered cell capture interface, PACE-Chip, which integrates click chemistry at the molecular level, nanofiber-like M13 phage scaffolds at the interfacial microscale, and herringbone structures at the device macroscale, achieving synergistic enhancement of both cell binding kinetics or affinity. The PACE-Chip exhibited 294% higher binding strength and 181-fold faster binding kinetics compared to its two-dimensional counterpart, enabling the highly efficient isolation of target cells from complex blood matrices down to the single-cell level. Further analysis revealed that excessive phage length compromises performance due to entropic and structural penalties, highlighting the multiscale trade-off between multivalency and conformational stability.